Host MHC class I molecules modulate in vivo expression of a NK cell receptor

Franz M. Karlhofer, Rosemarie Hunziker, Amy Reichlin, David H. Margulies, Wayne M. Yokoyama

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


Target cell expression of certain MHC class I molecules correlates with resistance to lysis by NK cells. To explain this correlation, one hypothesis states that NK cells may possess two types of receptors; one may activate NK cells whereas another, specific for target cell MHC class I molecules, may inhibit natural killing by transducing negative signals. The cell surface molecule, Ly-49, is expressed on an NK cell subpopulation (15% to 20%) in spleens from C57BL/6 (H-2b) mice. Previously, we showed that lysis by Ly- 49+ IL-2-activated NK cells was globally inhibited when targets expressed either H-2D(d) or an H-2(k)-class I molecule, consistent with the hypothesis that Ly-49 is an inhibitory NK cell receptor that engages these MHC class I molecules. We now have determined the influence of specific host MHC class I molecules on Ly-49 expression. In two-color flow cytometric examination of splenic cells, Ly-49+ NK1.1+ cells were undetectable in MHC-congenic strains expressing D(d) or D(k), in C57BL/6 mice transgenic for membrane- bound D(d), and in B10.D2(dm1) mice. These data establish that D(d) itself is sufficient for this effect and suggest that Ly-49 engages D(d)-α1/α2 domains. Cross-linking of Ly-49 with membrane-bound D(d) may be required because Ly-49+ NK1.1+ cells were readily detectable in C57BL/6 strains transgenic for soluble forms of D(d). To examine whether this effect could be the result of down-regulation of Ly-49 expression or negative selection of Ly-49+ cells, we determined Ly-49 expression on highly purified, freshly isolated NK cell populations (>90% NK1.1+ CD3- cells). These experiments demonstrated that Ly-49+ cells were present in normal numbers but that Ly- 49 expression was markedly decreased in congenic mice expressing H-2D(d) or D(k), and in the strain transgenic for membrane-bound H-2D(d). Thus, expression of a putative MHC class I-specific NK cell receptor is modulated by its apparent interaction with α1/α2 domains of host MHC class I molecules.

Original languageEnglish
Pages (from-to)2407-2416
Number of pages10
JournalJournal of Immunology
Issue number6
StatePublished - Sep 15 1994


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